Approximately 100 million people are infected with Wuchereria bancrofti, a mosquito-transmitted nematode parasite that causes deforming lymphatic filariasis in the tropics. Improved therapies and diagnostic methods have led to new thinking about lymphatic filariasis (LF) and the realization that it should be possible to interrupt transmission and eliminate this major public health problem by repeated cycles of mass drug administration (MDA). Egypt was one of the first countries in the world to implement a national program for elimination of lymphatic filariasis (PELF) based on this strategy. Our current ICIDR has worked to document the impact of the Egyptian PELF on filariasis prevalence and transmission in sentinel villages, and we have conducted research on the value of different tools for monitoring progress in ELF programs. This new ICIDR proposal is a natural extension of that work. In addition to the current cohesive group of researchers with different scientific backgrounds (medical epidemiology, immunology, molecular biology, and entomology) at Washington University, Smith College, and the RTC at Ain Shams University (Cairo), the new project adds a strong research group at Erasmus MC (Rotterdam) with expertise in modeling LF transmission and assessing the impact of control measures. The new ICIDR program will begin approximately one year after the 5th and final round of MDA in the Egyptian PELF (completed in October, 2004). The program is comprised of two interrelated projects: Project 1 will use the best available diagnostic tools in extensive field studies to assess whether filariasis has been eliminated in Egypt;materials and data collected in the field will be used in Project 2. Project 2 is focused on development of new tools for monitoring PELFs (promoting the objectives of Project 1). We have assembled a strong package of Cores to support these Projects and strengthen research capacity at RTC. Our personnel, experience, and enthusiasm place us in an excellent position to conduct research that should directly benefit efforts to eliminate filariasis, not only in Egypt, but also in many other endemic countries around the world. PROJECT 1: Research for the Elimination of Lymphatic Filariasis (Weil, G.) PROJECT 1 DESCRIPTION (provided by applicant): Improved therapies and diagnostic methods have led to new thinking about lymphatic filariasis and the realization that it should be possible to interrupt transmission and eliminate this major public health problem by repeated, annual cycles of mass drug administration (MDA) with new single dose combination drug regimens. Egypt was one of the first countries to implement a national program for elimination of lymphatic filariasis (PELF) based on MDA (annual distribution of diethylcarbamazine and albendazole, initiated in September 2000). The Egyptian Ministry of Health and Population (MOHP) completed its 5th and final round of MDA in October, 2004. Our detailed studies of sentinel villages during the current ICIDR project showed that the initial years of the MDA program had a major impact on LF prevalence (microfilaremia and circulating antigenemia) and transmission parameters (using antibody prevalence rates in primary school children as a marker for exposure to the parasite and PCR detection of parasite DMA in mosquito pools to estimate mosquito infection rates). Indeed, it is likely that LF was eliminated by MDA in these villages. The new project is a natural extension (and major expansion) of that work. The new project takes advantage of the strong, multidisciplinary filariasis research team at RTC, Ain Shams University in Cairo. ICIDR personnel will work closely with the Egyptian Ministry of Health and Population to carry out this ambitious project with extensive field studies. This will be the first attempt to rigorously assess a national PELF on this scale and also the first to use a national ELF program as a research laboratory. We will explore strategies for managing late stages of a PELF, test elimination indicators, and test the hypothesis that filariasis has been eliminated in Egypt by 5 rounds of MDA. We will also assess the value of advanced diagnostic methods for detecting foci of continued transmission and for early detection of resurgent transmission following suspension of MDA. Lessons learned in Egypt will benefit PELFs around the world.